Prospective Clinical Integration of an Amplicon-Based Next-Generation Sequencing Method to Select Advanced Non-Small-Cell Lung Cancer Patients for Genotype-Tailored Treatments.

INTRODUCTION: A substantial fraction of non-small-cell lung cancers (NSCLCs) harbor targetable genetic alterations. In this study, we analyzed the feasibility and clinical utility of integrating a next-generation sequencing (NGS) panel into our routine lung cancer molecular subtyping algorithm. PATIENTS AND METHODS: After routine pathologic and molecular subtyping, we implemented an amplicon-based gene panel for DNA analysis covering mutational hot spots in 22 cancer genes in consecutive advanced-stage NSCLCs. RESULTS: We analyzed 109 tumors using NGS between December 2014 and January 2016. Fifty-six patients (51%) were treatment-naive and 82 (75%) had lung adenocarcinomas. In 89 cases (82%), we used samples derived from lung cancer diagnostic procedures. We obtained successful sequencing results in 95 cases (87%). As part of our routine lung cancer molecular subtyping protocol, single-gene testing for EGFR, ALK, and ROS1 was attempted in nonsquamous and 3 squamous-cell cancers (n = 92). Sixty-nine of 92 samples (75%) had sufficient tissue to complete ALK and ROS1 immunohistochemistry (IHC) and NGS. With the integration of the gene panel, 40 NSCLCs (37%) in the entire cohort and 30 NSCLCs (40%) fully tested for ALK and ROS1 IHC and NGS had actionable mutations. KRAS (24%) and EGFR (10%) were the most frequently mutated actionable genes. Ten patients (9%) received matched targeted therapies, 6 (5%) in clinical trials. CONCLUSION: The combination of IHC tests for ALK and ROS1 and amplicon-based NGS is applicable in routine clinical practice, enabling patient selection for genotype-tailored treatments.

Regresión de calcificaciones vasculares en paciente con calcifilaxia / Regression of vascular calcification in a patient with calciphylaxis

No disponible

Nighttime blood pressure fall in renal disease patients.

OBJECTIVE: There are controversial reports in the prevalence of abnormal nighttime blood pressure fall in renal patients. It has been evaluated nocturnal BP in renal patients using 24 h blood pressure monitoring (ABPM) in comparison with nontreated control subjects either normotensives or hypertensives. DESIGN AND METHODS: It has been reviewed 137 ABPM studies performed in renal patients (47.8 +/- 15.4 years, 76 men and 61 women). The control group includes 119 subjects without kidney disease, 65 were normotensives, and 49 were hypertensives, aged 46.8 +/- 12.1 years, 59 men and 60 women. The ambulatory BP was measured noninvasively for 24h by the SpaceLabs 90207 device programmed to measure BP every 15 min during daytime and every 20 min during nighttime. The definition of daytime and nighttime was made on the basis of wakefulness and sleep or bed rest periods, obtained from a diary kept by each subject. RESULTS: SBP, but not DBP, was higher (133.9/81.7) in renal disease patients when compared to nonrenal subjects (127.9/80.8, p < 0.01). When the control group was split into normotensive and hypertensive patients there were still significant differences, but hypertensives had higher BP than renal disease patients (139.0/89.7, p < 0.05). Nocturnal SBP fall in renal disease patients was reduced (5.8%, p < 0.001) and so was DBP fall (11.1%, p < 0.001) compared with the overall nonrenal patients sample (SBP 10.8; DBP 15.3%). The frequency of nondipper status in renal disease patients (39.6%) was higher than in control patients (18.4%, p < 0.001). Nontreated normotensive renal disease patients did not show any difference in either SBP or DBP nighttime fall with respect to control normotensives. Neither do nontreated hypertensive renal patients as compared with control hypertensives. There were not differences between proteinuric and nonproteinuric patients in nocturnal BP fall. The same result was obtained when hypertensive and normotensive nontreated renal patients were compared. The presence of renal failure did not induce a reduction of nocturnal BP fall. Most of treated renal patients were mainly receiving drug therapy during the morning and frequently this was the single daily dose. CONCLUSIONS: Altered diurnal rhythm should not be considered as a usual complication of renal disease. Inadequate antihypertensive pharmacotherapy could be related to the abnormalities of nighttime BP fall when it is detected.